Improving Biomanufacturing Resilience in an Uncertain Future

In this interactive panel discussion, The Next Pandemic: Biopharma's Opportunities and Obligations, three speakers discussed the role and value of collaborations and what strategies can be used to help improve biomanufacturing resilience in an unpredictable but promising future. This article outlines some of the key takeaways from the conversation, including how the industry was transformed by the recent public health crisis and what new considerations stakeholders will have to account for over the next several years.

Grading the Global Pandemic Response

When the coronavirus pandemic began, there were limited plans in place to develop products at the pace needed to combat a rapidly spreading virus. Instead, an all-hands-on-deck approach ensued, with a historical convergence of private and public entities to develop new vaccines and therapies targeting coronavirus infections. A majority of the funding for these activities came from governmental sources, with the largest contribution made by the U.S. government to support late-stage vaccine development and expansion of manufacturing capacity through Operation Warp Speed and the Biomedical Advanced Research and Development Authority¹.

Although the effort fell short of its original goal of 300 million doses by January 2021, the pace at which drug companies were able to produce an effective vaccine for delivery shattered the status quo for drug development timelines. Panel participant Jon Weaver, president and CEO of Massachusetts Biomedical Initiatives (MBI), said this by itself was an incredible accomplishment and the reason he gave an A-/B+ when asked by Bioprocess Online host Matt Pillar to grade the global vaccine therapeutic preparedness development and response.

“To me, the fact that the industry was already set up to move innovation forward on their own using technologies out of small startups and academia as well as existing relationships with government to build partnerships and get through the regulatory process makes what happened that much more miraculous,” Weaver said. MBI helped over 100 startups acquire the space and development resources they need through its novel approach to collaboration among academic business and government communities in Massachusetts and beyond. “Typically, we’re at an early stage, where it takes companies seven to 10 years and a billion dollars [to bring a drug to market],” he continued. “But these technologies were already so close that we were able to get [the vaccines] out very quickly. That is something we should all be pretty proud of.”

Another panelist, Jeff Wolf, founder and CEO of Heat Biologics Inc., an emerging biotechnology company focused on the field of immunotherapy, acknowledged this accomplishment but added that a deeper look at what went wrong and, more importantly, what went right is critical to the success of future pandemic responses. He cited the Prepare for and Respond to Existing Viruses, Emerging New Threats, and Pandemics Act (PREVENT Pandemics Act) as a viable step in the right direction. As described in a press release, the PREVENT Pandemics Act is bipartisan legislation focused on strengthening the nation’s public health and medical preparedness and response systems in the wake of the COVID-19 pandemic². With the fate of this bill yet to be determined and many parts of the world still waiting on vaccine distribution, Wolf offered a pandemic response grade of ‘incomplete.’ “As we see new emerging variants not addressed by existing vaccines, new ones are not on the horizon because funding has been curtailed,” he explained, referring to the U.S. recently suspending funding. “That was truly a mistake.”

Panelist Adrian Wallis, chief strategy and technology officer at Lakes BioScience, a UK collaborative aimed at building a premier biopharma contract development and manufacturing operation in its nation, echoed Wolf’s comments that, despite some successes, there are many areas the UK could still improve upon. “Although we could never claim to be perfect given the death toll here, I think the regulatory authorities in the UK have performed excellently in terms of getting vaccines and initial therapeutic antibodies to patients,” he explained. “We’ve also learned a lot about the supply chain and have identified some areas of thin supply chain response, so we need to address that.” Wallace added, though, that what he hopes the UK does not do as infection numbers drop is lose focus and revert back to pre-COVID norms. “We have to learn from the last two years and prepare for the next pandemic because there will be another pandemic. Public funding and government commitment need to be focused on delivering strategies and enabling long-term resilience.”

The Fundamental Role of Public/Private Partnerships

Given the accomplishments of public/private partnerships (PPPs) over the last two years, such as the Operation Warp Speed initiative, an important part of maintaining the momentum is taking a closer look at what needs to be done to facilitate future PPPs, Wallis confirmed. Specifically, how does a biopharma company reconcile the short-term opportunity that a public health emergency presents with managing the existing mission of their business? And how can they leverage public resources to enable those efforts? These are the questions Pillar presented to his expert panel, which became especially pertinent after an audience poll revealed that nearly half of attendees were not leveraging partnerships or funding from public health agencies to support the development of therapeutic candidates in their pipelines.

“The role for [the public sector] should be to come in when the capitalist system can support [long- term initiatives aimed at public health emergencies] with adequate funding mechanisms in place for biotech companies to pursue commercial drugs and programs,” explained Wolf. “But something like this that was so unexpected―and requires long-term development efforts for events that may or may not ever happen―is not a place where most private companies can put their cash, especially small private companies. We, as a biotech company, need to focus on programs with commercial application that aren't so binary; but if we have a technology that could lend itself to something like COVID-19, companies like ours need financial support from the [governmental] agencies to apply those programs to threats that were unexpected.”

There are several mechanisms currently in place that early-stage biopharma companies can utilize as public partnerships. For example, federal government seed initiatives, such as the Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs, “encourage domestic small businesses to engage in Federal Research/Research and Development (R/R&D) with the potential for commercialization³.” Federal funding to support academic research programs is another source for early innovation that may not be market driven but can be leveraged by industry to respond to public health emergencies. However, the limited number of event attendees pursuing public funding could possibly be a reflection of the complexities associated with obtaining it. When asked where companies in need of funding can go for guidance, Weaver explained there is a network of support available, not only the aforementioned SBIR, but also consultants specializing in this area and even those within the industry who have walked this path before. “Find the program officer in your space within the federal government and start that dialogue with them,” he explained. “If they’re aware of the technology you have, there’s likely a host of opportunities available for you.”

Although funding is a critical component of developing innovative products, getting them to the general public and patients who need them is a major bottleneck that has continued to narrow since the onset of the pandemic. Efforts to address the vulnerabilities exposed by COVID-19, such as the PREVENT Pandemics Act, could create a more robust infrastructure and supply chain for pandemic response. However, the question of what can and should the biopharma industry do to strengthen its performance and provide better outcomes to patients still needs to be addressed.

Future Success Depends on Flexible, Agile Manufacturing

The increasingly complex and diverse pipeline of new modalities emerging over the last decade already began to reveal the inadequacies of traditional pharmaceutical manufacturing platforms and their inability to respond quickly to changes in product type and demand. However, this issue catapulted to the forefront during the pandemic when most biopharmaceutical manufacturers lacked the capabilities and capacity necessary to manufacture COVID-19 vaccines on such a large scale in such a little amount of time. This is a shortcoming that the FDA’s Center for Biologics Evaluation and Research (CBER) Director Peter Marks, MD, PhD, noted in a March 2020 conference about manufacturing individualized therapeutics before anyone realized the effect it would have over the next two years. In his remarks, Dr. Marks said, “We are still making vectors much the same way we made them at the turn of the millennium, and we really need to figure out how to move that forward. Right now, we have one sweet spot, which is the ‘grande’ size⁴.”

Referring to the larger size one would order at a coffee shop, Dr. Marks implied that the industry must adopt methods for efficient manufacturing in lower volumes in order to accommodate the direction of the industry toward smaller populations with unmet medical needs. Guest speakers in Bioprocess Online’s panel discussion echoed this sentiment during the conversation about enabling resiliency, with flexible, agile manufacturing solutions leading the charge. “The biggest thing [MBI] is seeing is a focus toward resiliency,” explained Weaver. “Companies are trying to establish local facilities while also looking at how they can design those facilities to make them more resilient within themselves, incorporating flexible, portable, disposable technologies that allow them to quickly adapt to different processes. There is a shift away from large stainless-steel vats and into products like those offered by companies like Cytiva, which has a whole platform of manufacturing technologies that allow companies to be more flexible.”

As noted in a recent survey about global biopharma resiliency, increasing domestic production, potentially with portable, flexible manufacturing technologies and solutions, is one strategy, but also securing stronger networks with suppliers globally, as this could offer even more agility in a company’s supply chain. “One thing to highlight is that the notion of ensuring robust supply chain capability through better considerations around agility within the supply chain is really important, but there is still a place for just-in-time because, for me, those two things are not mutually exclusive,” explained Wallis. “What we’ve seen in the UK is a need to increase manufacturing capability here in order to shorten the supply chain, and that’s where Lakes BioScience will sit very clearly. There’s a danger of throwing the baby out with the bath water with resilience and overstock versus just-in-time, so we need to be clearer about supply chain capabilities and engaging in more collaborative working, as I think more companies are working toward having partnerships in place within the supply chain to make sure that they're not short-handed.”

Heat Biologics’ cellular vaccine platform RapidVax®, which is purpose built to target known and unknown emerging biological threats, offers an example of a flexible technology that industry can utilize for rapid scale-up during a pandemic⁵. Launched via a task force of experts from academia and former government officials and facilitated by a favorable regulatory environment, this project represents the key elements necessary to create an agile development and manufacturing response to population- level threats of infectious disease. “You need to have a system that can respond quickly, not only in terms of building the actual drug to respond but also manufacturing distribution and, most importantly, getting enough supply to start clinical trials immediately,” explained Wolf. “That’s what RapidVax® is focused on because the timer doesn’t start until you’ve gone through the clinic.”

Weaver reiterated the importance of creating manufacturing autonomy in the early phases of development, especially for the emerging pharma MBI helps support. “We’re now extending ourselves to include scale-up space where companies can really start to grow through a Series A round and beyond,” he stated. “We’re designing all of that space with an eye toward manufacturing, so companies can implement their own process development capabilities and even begin Phase 1 or Phase 2 clinical trials, making it easier for them to get through those early stages and then scale in one location with great support throughout the process.”

Balancing Risk vs Reward

Even after two years, the pressure on the biopharmaceutical industry to develop innovative products and technologies to combat the ongoing pandemic has not lifted. In fact, it is likely only heightened now that the world has seen what a lack of readiness can do in the face of a deadly pandemic. Nevertheless, the expert panel agreed: biomanufacturing resilience calls on collaborations across the public and private landscape, with both parties sharing the balance of risk and reward in the name of a brighter and healthier future.

Watch the complete on-demand webcast to hear the panel’s thoughts on other key areas, such as other emerging technologies and modalities, what role therapeutics play in future public health emergencies, and the potential impact of the PREVENT Pandemics Act.